Pfizer's Sildenafil Citrate (registered trademark Viagra) possesses pharmacological mechanism to increase 3′,5′-cyclic guanosine monophosphate (cGMP) through inhibiting phosphodiesterase (PDE). Prior studies directly proves that the role of cGMP and PKG-1 signaling could reveal suppression of ventricular hypertrophy. Clinical efficacy of Sildenafil Citrate is used in treatment of male sexual function and in improvement on pulmonary arterial hypertension (PAH), erectile dysfunction (ED), and urinary symptoms in men with benign prostatic hyperplasia (BPH) with lower urinary tract symptom (LUTS) or depression.
Although World Patent No. WO 9849166 A1 discloses that the synthesis method of Sildenafil, and the other with 2-pentanone and diethyl oxalate as raw material can be synthesized Sildenafil, such methods of synthesis are usually only based the pyrazolo[4,3d]pyrimidin-7-one moiety structure of Sildenafil compounds. The Sildenafil salt disclosed in these specification is the general type of pharmaceutically acceptable salt. Both EP 2024369 and EP 1779852, and U.S. Pat. No. 7,618,976 disclosed the synthesis method of Sildenafil Citrate. U.S. Pat. No. 6,087,362 disclosed the pharmaceutical composition which is oral administration of Apomorphine and Sildenafil, or Sildenafil and cyclodextrin.
The xanthine based derivative compound of KMUP-1 has indicated that its activity includes the activation of endothelial NOS (eNOS), associated activation of soluble guanylyl cyclase (sGC) and inhibition of phosphodiesterase-5A (a PDE-5A inhibitor). It is already proven that KMUP-1 can effect the cyclic adenosine monophosphate, (cAMP)/protein kinase A (PKA) and cGMP/PKG signaling pathways thereby activating sGC (Wu et al., 2004). KMUP-1 has been described to have not only induce eNOS release but also have the resembling NO donor effects. For many years study, the inventor has found that KMUP-1 compound has some pleiotropic activities. This invention relates to treating the hypertension as US APPLICATION No. US 20080312249, on the treatment of benign prostatic hyperplasia as No. US 20050085486, and treating pulmonary hypertension as US 20080312249.